Clinical significance of circulating tumor cells identified by cell-surface vimentin in pancreatic cancer.

Abstract

e14562 Background: Identification of circulating tumor cells (CTCs) largely rely on epithelial tumor cell marker. Here we sought to interrogate whether cell-surface vimentin could be a biomarker for isolating CTCs potentially with mesenchymal phenotype in pancreatic ductal adenocarcinoma (PDAC). Methods: In total, 100 PDAC patients, 16 patients with intraductal papillary mucinous neoplasm (IPMN), and 30 healthy individuals were enrolled between December 2016 and November 2017. Potential CTCs were captured in 4 ml blood samples by vimentin antibody-coated microfluidic chip. CTCs were defined as vimentin+CD45-Hoechst+. Results: In vitro experiment showed that vimentin was highly expressed on the surface of pancreatic tumor cells with mesenchymal phenotype. Overall, vimentin+ CTCs were detected in 76% of patients with PDAC, but only in 2 out 30 healthy donors. Besides, five patients (31.3%) with IPMN had vimentin+ CTCs, and 10 CTCs were identified in one case. Using a cut-off value of two cells/4 ml of blood, 65% PDAC patients were positive for vimentin+ CTCs , while the positivity rates for the patients with IPMN and the healthy controls were 25% and 0%, respectively. Combined vimentin+ CTCs and CA19-9 offered a favorable diagnostic potency with area under curve of 0.968. Vimentin+ CTCs counts correlated with change of tumor burden for patients undergoing resection ( P < 0.01). Significant reduction of CTCs counts was observed after chemotherapy for subjects responding to treatment ( P < 0.05). The paired analysis showed that CTC counts was higher in portal vein blood than peripheral blood for 10 patients with available samples ( P < 0.05). Patients with 2 or more CTCs detected had more advanced disease and poorer differentiated tumor. In addition, preoperative higher CTCs counts correlated with shortened recurrence-free survival (Log-rank test: P = 0.02). Conclusions: Vimentin+ CTCs serves as a reliable biomarker in pancreatic cancer. The enrichment of potential mesenchymal CTCs could complement the strategy capturing epithelial CTCs, and provides a way to more thoroughly interrogate the biology and clinical significance of CTCs in PDAC.